Citations

AbstractConvalescent plasma, collected from donors who have recovered from a pathogen of interest, has been used to treat infectious diseases, particularly in times of outbreak, when alternative therapies were unavailable. The COVID‐19 pandemic revived interest in the use of convalescent plasma. Large observational studies and clinical trials that were executed during the pandemic provided insight into how to use convalescent plasma, whereby high levels of antibodies against the pathogen of interest and administration early within the time course of the disease are critical for optimal therapeutic effect. Several studies have shown outpatient administration of COVID‐19 convalescent plasma (CCP) to be both safe and effective, preventing clinical progression in patients when administered within the first week of COVID‐19. The United States Food and Drug Administration expanded its emergency use authorization (EUA) to allow for the administration of CCP in an outpatient setting in December 2021, at least for immunocompromised patients or those on immunosuppressive therapy. Outpatient transfusion of CCP and infusion of monoclonal antibody therapies for a highly transmissible infectious disease introduces nuanced challenges related to infection prevention. Drawing on our experiences with the clinical and research use of CCP, we describe the logistical considerations and workflow spanning procurement of qualified products, infrastructure, staffing, transfusion, and associated management of adverse events. The purpose of this description is to facilitate the efforts of others intent on establishing outpatient transfusion programs for CCP and other antibody‐based therapies.

Introduction: Intravenous alteplase (tissue plasminogen activator) has been shown to be cost-effective due to savings in long-term disability. In October of 2005, an increased DRG payment to hospitals for alteplase-treated stroke patients was introduced. We sought to describe the trends in the cost of alteplase over time, in comparison to trends in hospital reimbursement in the United States. Methods: Utilizing publicly available information on the Centers for Medicare and Medicaid Services (CMS) website (www.cms.gov), we obtained CMS quarterly payment amounts between 1/1/2005-10/1/2014 for alteplase, listed as “alteplase recombinant, per mg.” CMS payment amounts are the manufacturer’s average sales price (ASP) + 6% until 4/2014, when it was lowered to + 4.3%. Estimates for DRG base payments were calculated within MEDPAR for FY 2006 (DRG 559) and 2013 (MS DRGs 61,62, and 63) as: (DRG relative weights) x (standardized operating and capital amount). The Consumer Price Index (CPI) was also queried for all prescription drugs, urban areas, during the same study period as reference. Results: The CMS payment amount for alteplase/mg was $30.50 in 1/2005, and $64.30 in 10/2014. Trends in the CMS payment amounts for alteplase increased by 111% between 2005-2014, shown in the Figure. The CPI for all prescription drugs increased by 30.2% in the same time frame. The base payment for alteplase-treated stroke admissions was $11,173 in 2006, and $12,064 in 2013, an 8% increase. Discussion: We found a striking increase in the cost of alteplase over the last decade, with a 100mg vial now with a CMS payment of ∼$6400, a more than 100% increase over ten years. During the same timeframe, the DRG base payment to hospitals increased by only 8%, and alteplase cost increased from 27% of the payment in 2006 to 53% in 2013. Researchers and stroke physicians should be aware of these changes in drug costs and their impact on cost-effectiveness analyses.

Background Meeting Recruitment goals in a research study can be challenging. Recruitment for pedigree-based research, in which data and DNA are collected from genetically important family members, is especially difficult. The Familial Intracranial Aneurysm (FIA) study is a multicenter international study whose goal is to identify genetic and other risk factors for the formation and rupture of intracranial aneurysms (IAs). The chosen sites for the study are major referral centers for the diagnosis and treatment of IAs. In this analysis, we sought to determine what factors caused a recruited family to be incomplete, and what impact the methods used in identifying families had on the successful completion of family enrollment. Methods Three recruitment strategies were utilized to identify and enroll families: prospective monitoring of every new case of IA, subarachnoid hemorrhage, or intracranial hemorrhage; retrospective review of IA cases; and advertisement on the Internet, in scientific journals, and at professional meetings. An unexpected additional source of recruitment was exposure to the study through the news media. To help with public accessibility to the study, a web site and toll free number were established. Families were eligible for the study if they fit one of 4 patterns: [1] ≥2 living siblings affected with IA; [2] ≥2 affected siblings, 1 living and 1 genotype reconstructed from living spouse and children; [3] ≥3 affected members, 2 living and 1 reconstructed; [4] ≥ 3 affected members, 1 living, ≥1 reconstructed, and ≥1 living connecting relative. Exclusion criteria included fusiform-shaped IA; IA part of an AVM; family history of polycystic kidney disease; Ehlers-Danlos, Marfan, or moyamoya syndrome; fibromuscular dysplasia; or failure to obtain informed consent. Results Between 8/2002 and 10/2007, 3771 IA patients were screened for family history, and 681 potential families were identified, of which 441 successfully completed enrollment. There were 240 families which did not complete enrollment, due to refusal to participate (97), inability to locate needed relatives (87), exclusion criteria (50), no reason documented (5), and duplication (1 recruited at two sites). Completion of study enrollment was not significantly different by recruitment category (p=.17): 191 of 311 prospectively-recruited (61%), 66 of 89 retrospective (74%), 95 of 145 advertisement (66%), and 89 of 136 methods not documented (65%) families successfully completed enrollment. Conclusion In our study, the major reason for family exclusion was the inability to enroll needed family members, through refusal or failure to locate. All three methods used to identify potential families were successful in completing eligible families. The combination of recruitment strategies can be effectively implemented in future studies.

ABSTRACTBackgroundIntracavernosal injections (ICI) are a well-established treatment option for men with erectile dysfunction (ED); however, the anticipation of pain with injection remains a significant barrier to the use of ICI.AimTo evaluate the patient-anticipated degree of pain versus the experienced degree of pain pre- and post-ICI in men undergoing their first injection with an erectile agent.MethodsWe studied 51 patients who underwent their first ICI in our men’s health clinic. Anticipated needle-associated pain was judged with a pre-injection score, and pain experienced during the injection was judged with a post-injection score. All patients graded their pre- and post-ICI pain using a standard 10-point scale (0–10).OutcomesPre- and post-ICI pain was defined with the visual analogue scale (0–10) in men undergoing their first penile injection.ResultsMedians and interquartile ranges (IQRs) of the patients’ age [65 years (54.5–68.0)], pre-injection pain [5 (4–7)], and post-injection pain [1 (1–2)] were recorded. Most men in the study had erectile dysfunction (68.6%) and/or Peyronie’s Disease (64.7%). The average pre-injection prediction pain score was 5.45 ± 2.15; the average post-injection perceived pain score was 1.20 ± 0.73. Thus, there was an average discrepancy of over 4 points in predicted pain vs perceived pain. A paired t-test was performed which showed a statistically significant difference between pre- and post-injection scores (P < .05). A Wilcoxson Signed Rank Test showed statistical significance in the difference between pre- and post-injection pain scores (P < .05).Clinical ImplicationsICI is a safe, effective treatment for patients with ED and is associated with significantly less pain than is anticipated by patients.Strengths & LimitationsThis is the first report to describe the discrepancy between pre-ICI anticipated pain and post-ICI experienced pain. Limitations include an overall small sample size.ConclusionPatients experience significantly less pain with ICI than they anticipate having. This represents an important factor to consider when counseling patients about available ED treatments.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals working with cancer survivors to ensure that each survivor’s complex and varied needs are addressed. The Guidelines provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment; recommendations to help promote healthful lifestyle behaviors, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes the recommendations regarding employment and return to work for cancer survivors that were added in the 2021 version of the NCCN Guidelines.

Abstract IntroductionRadiotherapy is considered standard of care for adjuvant peri-operative treatment of many spinal tumors, including those with instrumented fusion. Unfortunately, radiation treatment has been linked to increased risk of pseudoarthrosis. Newerfocused radiotherapy strategies with enhanced conformalitycould offer improved fusion rates for these patients, but this has not been confirmed.MethodsWe performed a retrospective analysis of patients at three tertiary care academic institutions withprimary and secondary spinal malignancies that underwent resection, instrumented fusion, and peri-operative radiotherapy. Two board certified neuro-radiologists used theLenke fusion score to grade fusion status at6 and 12-months after surgery. Secondary outcomes includedclinical pseudoarthrosis, wound complications, and the effect of radiation timing, radiobiological dose delivered, the use of photons versus protons, tumor type, tumor location,and use of autograft on fusion outcomes.ResultsAfter reviewof 1252 spinal tumor patients, there were 60 patients with at least 6 months follow-up that were included in our analyses. Twenty-five of these patients received focused radiotherapy,20 patients received conventional radiotherapy, and 15 patients were treated with protons. There was no significant difference between the groups for covariates such assmoking status,obesity, diabetes, intraoperative use of autograft, and use of peri-operative chemotherapy. There was a significantly higher rate of fusion for patients treated with focused radiotherapy compared to those treated with conventional radiotherapy at 6-months (64.0% versus 30.0%, Odds ratio: 4.15, p=0.036) and 12-months (80.0% versus 42.1%, OR: 5.50, p=0.022). There was a significantly higher rate of clinical pseudoarthrosis in the conventional radiotherapy cohortcompared to patients in the focused radiotherapy cohort (19.1% versus 0%,p=0.037). There was no difference in fusion outcomes for any of the secondary outcomes except for use of autograft. The use ofintra-operative autograft was associated with an improved fusion at 12-months (66.7% versus 37.5%, OR: 3.33, p=0.043). ConclusionFocused radiotherapy may be associated withan improved rate of fusion and clinical pseudoarthrosis when compared to conventional radiation delivery strategiesin patients with spinal tumors.Use of autograft at the time of surgery may be associated with improved 12-month fusion rates.Further large-scale prospective and randomized controlled studies are needed to better stratify the effects of radiation delivery modality in these patients.

AbstractBackgroundColony‐stimulating factor‐1 receptor (CSF1R)‐related leukoencephalopathy is a rapidly progressive neurodegenerative disease for which there is currently no cure. Hematopoietic stem cell transplantation (HSCT) has been proposed as a disease‐modifying treatment.ObjectiveThe objective of this study was to determine the effect of HSCT on disease progression.MethodsWe collected all available clinical data from a cohort of 7 patients with CSF1R‐related leukoencephalopathy who underwent HSCT at our institutions. Clinical data included detailed neurological examination by a board‐certified neurologist, serial cognitive screens, formal neuropsychological evaluations, and serial brain magnetic resonance imaging (MRI).ResultsOur patients had an average disease duration of 27.6 months at the time of transplant, and we have 87 months of total posttransplant follow‐up time (median, 11; range, 2–27). One patient died in the periprocedural period. The remaining patients showed a variable response to treatment, with 6 of 7 patients trending toward stabilization on motor examination, cognitive scores, and/or MRI abnormalities, especially with white matter lesion burden.ConclusionsThis is the largest series of patients with CSF1R‐related leukoencephalopathy receiving HSCT. We conclude that HSCT can stabilize the disease in some patients. Variability in patient responsiveness suggests that measures of disease heterogeneity and severity need to be considered when evaluating a patient's candidacy for transplant. HSCT appears to be the first disease‐modifying therapy for CSF1R‐related leukoencephalopathy. This milestone may serve as a foothold toward better understanding the disease's pathomechanism, thus providing new opportunities for better disease‐specific therapies. © 2021 International Parkinson and Movement Disorder Society